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苯基 - N - 叔丁基硝酮的全身给药可保护视网膜免受光损伤。

Systemic administration of phenyl-N-tert-butylnitrone protects the retina from light damage.

作者信息

Ranchon I, Chen S, Alvarez K, Anderson R E

机构信息

Department of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA.

出版信息

Invest Ophthalmol Vis Sci. 2001 May;42(6):1375-9.

Abstract

PURPOSE

This study was conducted to test the hypothesis that phenyl-N-tert-butylnitrone (PBN), a spin-trapping agent known to cross the blood-brain barrier and protect the brain from ischemia-reperfusion injury, is incorporated into the retina after intraperitoneal injection and protects photoreceptor cells from the damaging effects of constant visible light.

METHODS

Albino rats were injected intraperitoneally with PBN (aqueous solution) or water, or were not injected, and then were placed in constant light (2700 lux) for 24 hours. The incorporation of PBN into the retina was determined by high-performance liquid chromatography. Electroretinograms (ERGs) were recorded before light treatment and 1 and 15 days after the cessation of exposure to constant light. Eyes were taken for histology at each time point and outer nuclear layer (ONL) thickness determined.

RESULTS

PBN was incorporated into the retina after intraperitoneal injection. Both control (water-injected and uninjected) groups exposed to constant light maintained only 28% of ONL thickness and 20% of retinal function, compared with the unexposed control group. In contrast, the PBN-treated animals maintained 80% of ONL thickness and exhibited 87% of retinal function.

CONCLUSIONS

PBN protects the albino rat retina from the damaging effects of constant light stress. That light-induced and hereditary retinal degenerations share certain morphologic hallmarks and follow a similar apoptotic mechanism of degeneration raises the possibility of pharmacologic therapy for hereditary and environmentally induced neurodegenerative disorders.

摘要

目的

本研究旨在验证以下假说:苯基 - N - 叔丁基硝酮(PBN)是一种已知可穿越血脑屏障并保护大脑免受缺血再灌注损伤的自旋捕捉剂,腹腔注射后可进入视网膜,并保护光感受器细胞免受持续可见光的损伤作用。

方法

对白化大鼠腹腔注射PBN(水溶液)或水,或不进行注射,然后将其置于持续光照(2700勒克斯)下24小时。通过高效液相色谱法测定PBN在视网膜中的掺入情况。在光照处理前以及停止持续光照后1天和15天记录视网膜电图(ERG)。在每个时间点取眼进行组织学检查,并测定外核层(ONL)厚度。

结果

腹腔注射后PBN进入了视网膜。与未暴露的对照组相比,暴露于持续光照下的两个对照组(注射水和未注射)仅保留了28%的ONL厚度和20%的视网膜功能。相比之下,经PBN处理的动物保留了80%的ONL厚度,并表现出87%的视网膜功能。

结论

PBN可保护白化大鼠视网膜免受持续光照应激的损伤作用。光诱导性和遗传性视网膜变性具有某些形态学特征,并遵循相似的凋亡性变性机制,这增加了对遗传性和环境诱导性神经退行性疾病进行药物治疗的可能性。

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